Table 3 Drug-like properties of RC002 (Callophysin A), GA004 (Nigricanoside A), and GA006 (Nigricanoside A dimethyl ester) using Swiss-ADME
Properties | Description | RC002 (Callophysin A) | GA004 (Nigricanoside A) | GA006 (Nigricanoside A dimethyl ester) |
|---|---|---|---|---|
Physicochemical properties | Molecular weight | 322.36 g/mol | 873.08 g/mol | 901.13 |
Rotatable bonds | 3 | 36 | 38 | |
H-bond acceptor | 4 | 16 | 16 | |
H-bond donor | 3 | 10 | 8 | |
Total polar surface area (TPSA) | 76.56 Å2 | 273.36 Å2 | 251.36 Å2 | |
Lipophilicity (log Po/w) | XlogP3 | 0.44 | 2.69 | 3.34 |
Solubility | log S (ESOL) | − 2.38 (Soluble) | − 4.57 (Moderately soluble | − 5.02 (Moderately soluble) |
log S (Ali) | − 1.62 (Very soluble) | − 8.08 (Poorly soluble) | − 8.30 (Poorly soluble) | |
Pharmacokinetics | GI absorption | High | Low | Low |
BBB permeability | Yes | No | No | |
P-gp substrate | Yes | Yes | Yes | |
CYP1A2 inhibitor | No | No | No | |
CYP2C19 inhibitor | No | No | No | |
CYP2C9 inhibitor | No | No | No | |
CYP2D6 inhibitor | Yes | No | No | |
CYP3A4 inhibitor | No | No | No | |
Skin permeability (log Kp) | − 7.95 cm/s | − 9.72 cm/s | − 9.43 cm/s | |
Drug-likeness | Lipinski | Yes; 0 violation | No; 3 violations | No; 3 violations |
Veber | Yes | No; 2 violations | No; 2 violations | |
Bioavailability score | 0.55 | 0.11 | 0.17 | |
Medicinal chemistry | PAINS | 1 alert: indol_3yl_alk | 0 alert | 0 alert |
Brenk | 0 alert | 1 alert; isolated alkene | 2 alerts; isolated alkene; > 2 esters | |
Lead-likeness | Yes | No; 2 violations | No; 2 violations | |
Synthetic accessibility | 2.96 | 9.45 | 9.71 |